Aging and Severity of Hypertension Attenuate Endothelium-Dependent Renal Vascular Relaxation in Humans

Abstract

Abstract Endothelial dysfunction may be related to cardiovascular risk factors, such as aging, hypertension, and atherosclerosis. We investigated whether aging and hypertension independently alter endothelial function in the renal circulation in humans in the absence of abnormalities in lipid and glucose metabolism. l -Arginine (500 mg/kg over 30 minutes) was intravenously administered to 33 patients with essential hypertension and 35 normotensive subjects. The l -arginine–induced increases in renal plasma flow (10.1±0.8% versus 15.8±0.9%, P <.05) and plasma cGMP (53±4% versus 82±5%, P <.05) were significantly smaller in patients with essential hypertension than in the normotensive subjects. Multivariate stepwise regression analysis showed that age ( P <.0002) and the mean blood pressure ( P <.0001) were independently and negatively correlated with the renal plasma flow response to l -arginine. Age ( P <.002), mean blood pressure ( P <.0001), and male sex ( P <.05) were independently correlated with the l -arginine–induced increase in plasma cGMP. The peak change in plasma cGMP was significantly correlated with the l -arginine–induced increase in renal plasma flow ( r =.63, P <.001). These findings suggest that aging and hypertension may independently impair endothelium-dependent renovascular dilation and that this effect may be caused at least in part by a decrease in nitric oxide production.